title: Off-the-shelf human decellularized tissue-engineered heart valves in a non-human primate model.
abstract: Heart valve tissue engineering based on decellularized xenogenic or allogenic starter matrices has shown promising first clinical results. However, the availability of healthy homologous donor valves is limited and xenogenic materials are associated with infectious and immunologic risks. To address such limitations, biodegradable synthetic materials have been successfully used for the creation of living autologous tissue-engineered heart valves (TEHVs) in vitro. Since these classical tissue engineering technologies necessitate substantial infrastructure and logistics, we recently introduced decellularized TEHVs (dTEHVs), based on biodegradable synthetic materials and vascular-derived cells, and successfully created a potential off-the-shelf starter matrix for guided tissue regeneration. Here, we investigate the host repopulation capacity of such dTEHVs in a non-human primate model with up to 8 weeks follow-up. After minimally invasive delivery into the orthotopic pulmonary position, dTEHVs revealed mobile and thin leaflets after 8 weeks of follow-up. Furthermore, mild-moderate valvular insufficiency and relative leaflet shortening were detected. However, in comparison to the decellularized human native heart valve control - representing currently used homografts - dTEHVs showed remarkable rapid cellular repopulation. Given this substantial in situ remodeling capacity, these results suggest that human cell-derived bioengineered decellularized materials represent a promising and clinically relevant starter matrix for heart valve tissue engineering. These biomaterials may ultimately overcome the limitations of currently used valve replacements by providing homologous, non-immunogenic, off-the-shelf replacement constructs.
authors.affiliation: Swiss Center of Regenerative Medicine, University of Zürich, Zürich, Switzerland.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Weber
authors.forename: Petra E
authors.initials: PE
authors.lastname: Dijkman
authors.forename: Jacques
authors.initials: J
authors.lastname: Scherman
authors.forename: Bart
authors.initials: B
authors.lastname: Sanders
authors.forename: Maximilian Y
authors.initials: MY
authors.lastname: Emmert
authors.forename: Jürg
authors.initials: J
authors.lastname: Grünenfelder
authors.forename: Renier
authors.initials: R
authors.lastname: Verbeek
authors.forename: Mona
authors.initials: M
authors.lastname: Bracher
authors.forename: Melanie
authors.initials: M
authors.lastname: Black
authors.forename: Thomas
authors.initials: T
authors.lastname: Franz
authors.forename: Jeroen
authors.initials: J
authors.lastname: Kortsmit
authors.forename: Peter
authors.initials: P
authors.lastname: Modregger
authors.forename: Silvia
authors.initials: S
authors.lastname: Peter
authors.forename: Marco
authors.initials: M
authors.lastname: Stampanoni
authors.forename: Jérôme
authors.initials: J
authors.lastname: Robert
authors.forename: Debora
authors.initials: D
authors.lastname: Kehl
authors.forename: Marina
authors.initials: M
authors.lastname: van Doeselaar
authors.forename: Martin
authors.initials: M
authors.lastname: Schweiger
authors.forename: Chad E
authors.initials: CE
authors.lastname: Brokopp
authors.forename: Thomas
authors.initials: T
authors.lastname: Wälchli
authors.forename: Volkmar
authors.initials: V
authors.lastname: Falk
authors.forename: Peter
authors.initials: P
authors.lastname: Zilla
authors.forename: Anita
authors.initials: A
authors.lastname: Driessen-Mol
authors.forename: Frank P T
authors.initials: FP
authors.lastname: Baaijens
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hoerstrup
mesh_terms: D000368:Aged; D000818:Animals; D048430:Cell Shape; D004247:DNA / Q000378:metabolism; D004730:Endothelium, Vascular / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000648:ultrastructure; D006351:Heart Valves / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D020007:Implants, Experimental; D007368:Interferometry; D008855:Microscopy, Electron, Scanning; D023421:Models, Animal; D010641:Phenotype; D011323:Primates / Q000502:physiology*; D019919:Prosthesis Implantation; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D004247:DNA
keywords: Decellularization; Heart valve tissue engineering; Homologous valve replacement; Minimally invasive; Preclinical in vivo model; Tissue regeneration